The major objective of the alcoholism-related project in my laboratory is to investigate the interrelationships between the alterations that occur in phospholipid and energy metabolism in liver tissue from animals that are developing fatty liver and energy metabolism in liver tissue from animals that are developing fatty liver due to chronic alcohol administration. We have obtained evidence which suggests that the membrane environments of two mitochondrial enzymes, phosphlipase A2 and the proton translocating ATPase, are altered in mitochondria isolated from animals fed ethanol for an extended period. It is likely that te phospholipids which provide the microenvironment of these enzymes are being altered by the ethaol feeding. The project described in this proposal includes an analysis of the phospholipids in both mitochondria and microsomes. We plan to determine whether alcohol adminstration initates changes at the level of the endoplasmic reticulum which give rise to altered phospholipids in the mitochondrion. We ultimately hope to determine if there is a change in lipid metabolism within the endoplasmic reticulum that stimulates both the development of fatty liver and changes in phospholipid within the mitochondrion. We therefore plan to characterize the phospholipids in both endoplasmic reticulum and mitochondria from livers of animals on an alcohol containing diet to determine quantitatively the changes that occur in phospholipid composition tha are due to chronic alcohol administration. In addition to phospholipid analyses, the process of phospholipid transfer from the endoplasmic reticulum to the mitochondrion will be measured in liver tissue from alcoholic rats. If phospholipid analyses suggest that the monoacyl phospholipid reacylase system is affected by ethanol feeding then this activity will be measured directly in mitochondria from ethanol fed animals.